This program-Project is for the support of a group of integrated studies at the Massachusetts General Hospital leading to the improved survival of heart transplant recipients. In this initial phase, no clinical heart transplants are planned, as we believe it best to build our capabilities through the present program in an orderly manner first. The projects include the following: intensive study of orthotopic heart transplants in sheep with special reference to quantification of the early inflammatory reaction which emerges in the course of rejection; a new approach to the extracorporeal maintenance of hearts in optimal condition for study and for transplantation; a thorough exploration of a new concept for individualized immunosuppression on the basis of serial tests of immune responsiveness combined with immunological approaches to the diagnosis of rejection in dogs receiving heterotopic heart transplants and in kidney transplant patients (who will act for the present as surrogate heart recipients); an analysis of host-pathogen relationships in immunosuppressed patients and animals; a concerted attack on the important problem of presensitization to histocompatibility antigens of the transplant recipient including studies of suitable patients and of animals; and the evaluation of a new approach to cardiac assist by an implantable mechanical device.